Hyaluronan is one of high molecular weight glycosaminoglycans and is constituted by repeated .beta.-1,4 linked disaccharide units, each of the unit being composed of glucuronic acid linked to N-acetylglucosamine by a .beta.-1,3 bond (GlcUA.beta.1-3GlcNAc; GlcUA and GlcNAc represent glucuronic acid and N-acetylglucosamine, respectively). Hyaluronan is a characteristic constituent of the extracellular matrix at the early stage of morphogenesis of animals. Its synthesis is regulated spatially and temporally (Toole, B. P. (1981) Cell Biology of the Extracellular Matrix (Hey, E. D., ed.) pp. 259-294, Plenum, New York). Accumulation of hyaluronan on the cell surface is correlated with regulation of behavior of cells, particularly migration, adhesion, cure of wounds, infiltration of tumors, and the like (Turley, E. A. (1989) The Biology of Hyaluronan, Ciba Foundation Symposium 143, pp. 121-137; Wiley, Chichester, England; Knudson, W., Biswas, C., Li, X.-Q., Nemec, R. E., and Tool, B. P. (1989) The Biology of Hyaluronan, Ciba Foundation Symposium 143, pp. 150-169, Wiley, Chichester, England; Laurent, T. C., and Fraser, J. R. E. (1992) FASEB J. 6, 2397-2404; Kimata, K., Honma, Y., Okayama, M., Oguri, K., Hozumi, M., and Suzuki, S. (1983) Cancer Res. 43, 1347-1354).
Biosysthesis of hyaluronan has been widely studied using a procaryote, Streptococci. A recent report revealed that a structural gene of hyaluronan synthase derived from Streptococcus pyogenes which is a procaryote was isolated (DeAngelis, P. L., Papaconstantinou, J., and Weigel, P. H. (1993) J. Biol. Chem. 268, 19181-19184). In contrast, little is known about the biosynthesis mechanism of hyaluronan in eucaryotes. Attempts have been made to purify eucaryotic hyaluronan synthase. However, some reports showed that the obtained enzyme lost its activity (Mian, N. (1986) Biochem. J. 237, 343-357; Ng, K. F., and Schwartz, N. B. (1989) J. Biol. Chem. 264, 11776-11783; Klewes, L., Turley, E. A., and Prehm, P. (1993) Biochem. J. 290, 791-795). Any DNA encoding a polypeptide of eucaryotic hyaluronan synthase is not known.
If a polypeptide of hyaluronan synthase derived from eucaryotes, particularly human, and a DNA encoding it are obtained, they would be useful for treatments, including gene therapy, of diseases caused by decreased expression of hyaluronan in humans. In addition, these substances would also be useful for gene therapy for suppressing metastasis of cancer using an antisense DNA, RNA, or the like as well as development of hyaluronan synthase-specific inhibitors.